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1.  The development of a short instrument to identify common unmet needs in older people in general practice 
Background: No structured needs assessment tool exists that is appropriate for older people and also suitable for use in routine consultations in general practice.
Aims: To engage older people in the development of a brief, valid, practical, and acceptable instrument to help identify common unmet needs suitable for use in routine clinical practice in primary care.
Design of study: User involvement in a multi-stages approach to heuristic development.
Setting: General practices, voluntary groups, and community organisations in north and central London.
Method: Subjects included patients aged 65 years and over in purposively selected practices, voluntary organisations for older people in the same localities, community organisations involving older people, general practitioners and community nurses. Data were collected through mixed methodology interviews using a structured assessment tool (Camberwell Assessment of Need for the Elderly), a postal questionnaire, and focus groups. Synthesis and interpretation of results was done through a consensus conference followed by a Delphi process involving primary care professionals.
Results: Five domains of unmet need were identified as priority areas by all three data collection methods, the consensus conference, and the Delphi process: senses (vision and hearing), physical ability (mobility and falls), incontinence, cognition, and emotional distress (depression and anxiety) (SPICE).
Conclusions: Public involvement in the design of clinical tools allowed the development of a brief assessment instrument that could potentially identify common, important, and tractable unmet needs in older people.
PMCID: PMC1326109  PMID: 15588536
consumer involvement; elderly; needs; primary care
3.  Community based yoga classes for type 2 diabetes: an exploratory randomised controlled trial 
Background
Yoga is a popular therapy for diabetes but its efficacy is contested. The aim of this study was to explore the feasibility of researching community based yoga classes in Type 2 diabetes with a view to informing the design of a definitive, multi-centre trial
Methods
The study design was an exploratory randomised controlled trial with in-depth process evaluation. The setting was two multi-ethnic boroughs in London, UK; one with average and one with low mean socio-economic deprivation score. Classes were held at a sports centre or GP surgery. Participants were 59 people with Type 2 diabetes not taking insulin, recruited from general practice lists or opportunistically by general practice staff. The intervention group were offered 12 weeks of a twice-weekly 90-minute yoga class; the control group was a waiting list for the yoga classes. Both groups received advice and leaflets on healthy lifestyle and were encouraged to exercise.
Primary outcome measure was HbA1c. Secondary outcome measures included attendance, weight, waist circumference, lipid levels, blood pressure, UKPDS cardiovascular risk score, diabetes-related quality of life (ADDQoL), and self-efficacy. Process measures were attendance at yoga sessions, self-reported frequency of practice between taught sessions, and qualitative data (interviews with patients and therapists, ethnographic observation of the yoga classes, and analysis of documents including minutes of meetings, correspondence, and exercise plans).
Results
Despite broad inclusion criteria, around two-thirds of the patients on GP diabetic registers proved ineligible, and 90% of the remainder declined to participate. Mean age of participants was 60 +/- 10 years. Attendance at yoga classes was around 50%. Nobody did the exercises regularly at home. Yoga teachers felt that most participants were unsuitable for 'standard' yoga exercises because of limited flexibility, lack of basic fitness, co-morbidity, and lack of confidence. There was a small fall in HbA1c in the yoga group which was not statistically significant and which was not sustained six months later, and no significant change in other outcome measures.
Conclusion
The benefits of yoga in type 2 diabetes suggested in some previous studies were not confirmed. Possible explanations (apart from lack of efficacy) include recruitment challenges; practical and motivational barriers to class attendance; physical and motivational barriers to engaging in the exercises; inadequate intensity and/or duration of yoga intervention; and insufficient personalisation of exercises to individual needs. All these factors should be considered when designing future trials.
Trial registration
National Research Register (1410) and Current Controlled Trials (ISRCTN63637211).
doi:10.1186/1472-6963-9-33
PMCID: PMC2652459  PMID: 19228402
4.  A systematic review of mental disorder, suicide, and deliberate self harm in lesbian, gay and bisexual people 
BMC Psychiatry  2008;8:70.
Background
Lesbian, gay and bisexual (LGB) people may be at higher risk of mental disorders than heterosexual people.
Method
We conducted a systematic review and meta-analysis of the prevalence of mental disorder, substance misuse, suicide, suicidal ideation and deliberate self harm in LGB people. We searched Medline, Embase, PsycInfo, Cinahl, the Cochrane Library Database, the Web of Knowledge, the Applied Social Sciences Index and Abstracts, the International Bibliography of the Social Sciences, Sociological Abstracts, the Campbell Collaboration and grey literature databases for articles published January 1966 to April 2005. We also used Google and Google Scholar and contacted authors where necessary. We searched all terms related to homosexual, lesbian and bisexual people and all terms related to mental disorders, suicide, and deliberate self harm. We included papers on population based studies which contained concurrent heterosexual comparison groups and valid definition of sexual orientation and mental health outcomes.
Results
Of 13706 papers identified, 476 were initially selected and 28 (25 studies) met inclusion criteria. Only one study met all our four quality criteria and seven met three of these criteria. Data was extracted on 214,344 heterosexual and 11,971 non heterosexual people. Meta-analyses revealed a two fold excess in suicide attempts in lesbian, gay and bisexual people [pooled risk ratio for lifetime risk 2.47 (CI 1.87, 3.28)]. The risk for depression and anxiety disorders (over a period of 12 months or a lifetime) on meta-analyses were at least 1.5 times higher in lesbian, gay and bisexual people (RR range 1.54–2.58) and alcohol and other substance dependence over 12 months was also 1.5 times higher (RR range 1.51–4.00). Results were similar in both sexes but meta analyses revealed that lesbian and bisexual women were particularly at risk of substance dependence (alcohol 12 months: RR 4.00, CI 2.85, 5.61; drug dependence: RR 3.50, CI 1.87, 6.53; any substance use disorder RR 3.42, CI 1.97–5.92), while lifetime prevalence of suicide attempt was especially high in gay and bisexual men (RR 4.28, CI 2.32, 7.88).
Conclusion
LGB people are at higher risk of mental disorder, suicidal ideation, substance misuse, and deliberate self harm than heterosexual people.
doi:10.1186/1471-244X-8-70
PMCID: PMC2533652  PMID: 18706118
5.  Randomised controlled trial of an interactive multimedia decision aid on benign prostatic hypertrophy in primary care 
BMJ : British Medical Journal  2001;323(7311):493.
Objective
To determine whether a decision aid on benign prostatic hypertrophy influences decision making, health outcomes, and resource use.
Design
Randomised controlled trial.
Setting
33 general practices in the United Kingdom.
Participants
112 men with benign prostatic hypertrophy.
Intervention
Patients' decision aid consisting of an interactive multimedia programme with booklet and printed summary.
Outcome measures
Patients' and general practitioners' perceptions of who made the decision, decisional conflict scores, treatment choice and prostatectomy rate, American Urological Association symptom scale, costs, anxiety, utility, and general health status.
Results
Both patients and general practitioners found the decision aid acceptable. A higher proportion of patients (32% v 4%; mean difference 28%, 95% confidence interval 14% to 41%) and their general practitioners (46% v 25%; 21%, 3% to 40%) perceived that treatment decisions had been made mainly or only by patients in the intervention group compared with the control group. Patients in the intervention group had significantly lower decisional conflict scores than those in the control group at three months (2.3 v 2.6; −0.3, −0.5 to −0.1, P<0.01) and this was maintained at nine months. No differences were found between the groups for anxiety, general health status, prostatic symptoms, utility, or costs (excluding costs associated with the video disc equipment).
Conclusions
The decision aid reduced decisional conflict in men with benign prostatic hypertrophy, and the patients played a more active part in decision making. Such programmes could be delivered cheaply by the internet, and there are good arguments for coordinated investment in them, particularly for conditions in which patient utilities are important.
What is already known on this topicPatients want more information about their condition and treatment options, and many want to play an active part in decision makingDecision aids improve patients' knowledge of their conditions and treatment optionsWhat this study addsThe decision aid was highly acceptable to both the patients and their general practitionersDecisional conflict was reduced in the intervention groupPatients who viewed the programme played a more active part in the decision making process and were less anxious than control patientsSuch aids could be introduced throughout the NHS at relatively low cost by using the internet
PMCID: PMC48138  PMID: 11532845
6.  Randomised controlled trial of an interactive multimedia decision aid on hormone replacement therapy in primary care 
BMJ : British Medical Journal  2001;323(7311):490.
Objective
To determine whether a decision aid on hormone replacement therapy influences decision making and health outcomes.
Design
Randomised controlled trial.
Setting
26 general practices in the United Kingdom.
Participants
205 women considering hormone replacement therapy.
Intervention
Patients' decision aid consisting of an interactive multimedia programme with booklet and printed summary.
Outcome measures
Patients' and general practitioners' perceptions of who made the decision, decisional conflict, treatment choice, menopausal symptoms, costs, anxiety, and general health status.
Results
Both patients and general practitioners found the decision aid acceptable. At three months, mean scores for decisional conflict were significantly lower in the intervention group than in the control group (2.5 v 2.8; mean difference −0.3, 95% confidence interval −0.5 to −0.2); this difference was maintained during follow up. A higher proportion of general practitioners perceived that treatment decisions had been made “mainly or only” by the patient in the intervention group than in the control group (55% v 31%; 24%, 8% to 40%). At three months a lower proportion of women in the intervention group than in the control group were undecided about treatment (14% v 26%; −12%, −23% to −0.4%), and a higher proportion had decided against hormone replacement therapy (46% v 32%; 14%, 1% to 28%); these differences were no longer apparent by nine months. No differences were found between the groups for anxiety, use of health service resources, general health status, or utility. The higher costs of the intervention were largely due to the video disc technology used.
Conclusions
An interactive multimedia decision aid in the NHS would be popular with patients, reduce decisional conflict, and let patients play a more active part in decision making without increasing anxiety. The use of web based technology would reduce the cost of the intervention.
What is already known on this topicPatients want more information about their conditions and treatment options, and many want to play an active part in decision makingDecision aids improve patients' knowledge of their conditions and treatment optionsWhat this study addsThe decision aid was acceptable to both the patients and their general practitionersDecisional conflict was reduced in the intervention groupPatients who viewed the programme played a more active part in the decision making process and were no more anxious than control patientsSuch aids could be introduced throughout the NHS at relatively low cost by using the internet
PMCID: PMC48137  PMID: 11532844
7.  A multidisciplinary approach for improving services in primary care: randomised controlled trial of screening for haemoglobin disorders 
BMJ : British Medical Journal  1998;317(7161):788-791.
Objective: To investigate the feasibility of improving screening for carriers of haemoglobin disorders in general practice by using a nurse facilitator to work with primary care teams and the relevant haematology laboratories; to identify problems in communication between all those involved in delivering the service, and to implement solutions.
Design: Two year, practice based randomised controlled trial.
Setting: North London area where 29% of residents and 43% of births are in ethnic groups at risk for haemoglobin disorders.
Subjects: 26 of the 93 practices using the services of the area’s haematology laboratory agreed to take part and were randomly divided into control and intervention practices.
Main outcome measure: Change in number of requests for screening tests for haemoglobin disorders made by control and intervention practices in baseline and intervention years.
Results: The number of screening tests requested varied from 0-150 in the 93 practices in the baseline year. Study practices tended to have made a moderate number of requests (10-50) during this period. During the intervention year intervention practices made 292 more requests (99% increase) and control practices made 74 fewer requests (23% decrease; P=0.001 for difference in median change). Four practices, three of which were singlehanded, accounted for 75% of the increase. The number of requests from intervention practices, adjusted for baseline requests, was 3.2 times higher than control practices (P<0.0001).
Conclusion: General practitioners and practice nurses are willing to undertake a new genetic screening service (or expand an existing one) if they are persuaded that it benefits the health of a significant proportion of their practice population. They need appropriate tools (for example, information materials for carriers and groups at risk), and the laboratory must be sensitive to their needs. Preconceptional carrier screening and counselling need to be coupled with antenatal screening.
Key messagesMany couples at risk of conceiving a child with a haemoglobin disorder are identified too late in pregnancy for prenatal diagnosis to be acceptable to themThese couples need to be identified before conception, or as soon as they report a pregnancy to their general practitionerScreening for haemoglobin disorders in primary care can be enhancedA multidisciplinary approach and a haematology laboratory responsive to the needs of local practitioners are importantThe nurse facilitator was particularly successful in persuading singlehanded practitioners practising in areas with a high prevalence of ethnic minorities to increase their testing for carriers
PMCID: PMC28672  PMID: 9740569
8.  Pediatric melioidosis in Sarawak, Malaysia: Epidemiological, clinical and microbiological characteristics 
PLoS Neglected Tropical Diseases  2017;11(6):e0005650.
Background
Melioidosis is a serious, and potentially fatal community-acquired infection endemic to northern Australia and Southeast Asia, including Sarawak, Malaysia. The disease, caused by the usually intrinsically aminoglycoside-resistant Burkholderia pseudomallei, most commonly affects adults with predisposing risk factors. There are limited data on pediatric melioidosis in Sarawak.
Methods
A part prospective, part retrospective study of children aged <15 years with culture-confirmed melioidosis was conducted in the 3 major public hospitals in Central Sarawak between 2009 and 2014. We examined epidemiological, clinical and microbiological characteristics.
Findings
Forty-two patients were recruited during the 6-year study period. The overall annual incidence was estimated to be 4.1 per 100,000 children <15 years, with marked variation between districts. No children had pre-existing medical conditions. Twenty-three (55%) had disseminated disease, 10 (43%) of whom died. The commonest site of infection was the lungs, which occurred in 21 (50%) children. Other important sites of infection included lymph nodes, spleen, joints and lacrimal glands. Seven (17%) children had bacteremia with no overt focus of infection. Delays in diagnosis and in melioidosis-appropriate antibiotic treatment were observed in nearly 90% of children. Of the clinical isolates tested, 35/36 (97%) were susceptible to gentamicin. Of these, all 11 isolates that were genotyped were of a single multi-locus sequence type, ST881, and possessed the putative B. pseudomallei virulence determinants bimABp, fhaB3, and the YLF gene cluster.
Conclusions
Central Sarawak has a very high incidence of pediatric melioidosis, caused predominantly by gentamicin-susceptible B. pseudomallei strains. Children frequently presented with disseminated disease and had an alarmingly high death rate, despite the absence of any apparent predisposing risk factor.
Author summary
Melioidosis is a serious, and often fatal community-acquired infection endemic to Southeast Asia and northern Australia. It is caused by the environmental saprophyte Burkholderia pseudomallei, a bacterium that is intrinsically resistant to many commonly used antibiotics. Its presence in Sarawak, Malaysian Borneo, has been documented, and recently, a novel gentamicin-susceptible strain discovered. However, there are limited data on the burden and clinical characteristics of melioidosis in Sarawak, both in adults and in children. In this study, we comprehensively investigated all pediatric melioidosis cases in Central Sarawak over a 6-year period. We found that this region has a very high incidence of pediatric melioidosis, and that children frequently presented with disseminated disease and had high fatality rates, despite the absence of any predisposing risk factor. We confirmed that these infections were caused predominantly by gentamicin-susceptible B. pseudomallei strains. We also highlighted other undescribed epidemiological, clinical and microbiological features, which may help in the overall understanding of B. pseudomallei infections. We emphasized the importance of improving the awareness and recognition of melioidosis in children, both in Sarawak and in other endemic regions.
doi:10.1371/journal.pntd.0005650
PMCID: PMC5479590  PMID: 28599008
9.  Dipeptidyl peptidase-4 inhibitor decreases the risk of atrial fibrillation in patients with type 2 diabetes: a nationwide cohort study in Taiwan 
Background
Whether dipeptidyl peptidase-4 inhibitor (DPP4i) is associated with a lower risk of new-onset atrial fibrillation (AF) in patients with diabetes remains unclear. This study aimed to evaluate the risk of AF associated with use of DPP4i among a longitudinal cohort of patients with diabetes.
Methods
Over a 3-year period, 480,000 patients with diabetes were analyzed utilizing Taiwan’s National Health Insurance Research Database and 90,880 patients taking metformin as first-line therapy were enrolled. Patients were further divided into two groups: (1) DPP4i users: those taking DPP4i and (2) non-DPP4i users: those prescribed other hypoglycemic agents (HAs) as second-line drug. Study end point was defined by diagnosis of AF, addition of any third-line HA, or the end of the study period (December 31, 2013), whichever came first.
Results
A total of 16,017 DPP4i users and 74,863 non-DPP4i users were eligible for the study. For the DPP4i group, most patients were prescribed sitagliptin (n = 12,180; 76%). Among the non-DPP4i group, most patients took sulfonylurea (n = 60,606; 81%) as their second-line medication. DPP4i users were associated with a lower risk of new-onset AF compared with non-DPP4i users after propensity-score weighting (hazard ratio 0.65; P < 0.0001). Subgroup analysis showed that DPP4i user were associated with a lower risk of new-onset AF compared with non-DPP4i users in most subgroups. Multivariate analysis indicated that use of DPP4i was associated with lower risk of new-onset AF and age > 65 years, presence of hypertension, and ischemic heart disease were independent risk factors for new-onset AF.
Conclusions
Among patients with diabetes prescribed with metformin, the patients with DPP4i as second HA were associated with a lower risk of AF compared with the patients with other drugs as second HAs in real-world practice.
Electronic supplementary material
The online version of this article (10.1186/s12933-017-0640-5) contains supplementary material, which is available to authorized users.
doi:10.1186/s12933-017-0640-5
PMCID: PMC5735601  PMID: 29258504
Dipeptidyl peptidase-4 inhibitor; Type 2 diabetes mellitus; Atrial fibrillation
10.  Bleeding risk with dabigatran, rivaroxaban, warfarin, and antiplatelet agent in Asians with non-valvular atrial fibrillation 
Oncotarget  2017;8(58):98898-98917.
It is not understood if dabigatran or rivaroxaban are superior to antiplatelet agents (AA) for safety outcomes in Asians with non-valvular atrial fibrillation (NVAF). In this study we evaluated the bleeding risk of dabigatran, rivaroxaban, warfarin and AA in Asians with NVAF. This national retrospective cohort study analyzed 6,600, 3,167, 5,338 and 8,238 consecutive NVAF patients taking dabigatran, rivaroxaban, warfarin or AAs (including aspirin, clopidogrel or ticlopidine), respectively, from June 1, 2012 to December 31, 2013. Propensity-score weighting was used to balance covariates across study groups. Patients were followed until the first occurrence of any bleeding outcome or the end of the study. The CHA2DS2-VASc scores were 4.1±1.6, 4.1±1.6, 3.3±1.8 and 2.4±1.6 for the dabigatran, rivaroxaban, warfarin, and AA groups, respectively. There were 5,822 (88.2%) and 164 (5.2%) patients taking low dose dabigatran and rivaroxaban, respectively. Hazard ratios (95% confidence intervals) for dabigatran, rivaroxaban, or warfarin versus AA were: intracranial hemorrhage, 0.36 (0.23-0.57;PP=0.0037) and 1.34 (0.89-2.02;P=0.1664); gastrointestinal bleeding, 0.44 (0.32-0.59;PP=0.0189); and all hospitalized major bleeding, 0.41 (0.32-0.53;PP=0.0644) and 0.90 (0.70-1.16;P=0.4130) after adjustment. The risk reduction of all major bleeding for dabigatran versus AA persisted on subgroup analysis. In conclusion, we observed that dabiagtran was associated with a lower risk of all major bleeding in Asians with NVAF, whereas rivaroxaban had a similar risk of all major bleeding compared with antiplatelet agents after adjustment of comorbidities.
doi:10.18632/oncotarget.22026
PMCID: PMC5716776
atrial fibrillation; direct thrombin inhibitor; factor xa inhibitor; hemorrhage; warfarin
11.  Differential expression of CD44 and CD24 markers discriminates the epitheliod from the fibroblastoid subset in a sarcomatoid renal carcinoma cell line: evidence suggesting the existence of cancer stem cells in both subsets as studied with sorted cells 
Oncotarget  2017;8(9):15593-15609.
Epithelioid and fibroblastoid subsets coexist in the human sarcomatoid renal cell carcinoma (sRCC) cell line, RCC52, according to previous clonal studies. Herein, using monoclonal antibodies to CD44 and CD24 markers, we identified and isolated these two populations, and showed that CD44bright/CD24dim and CD44bright/CD24bright phenotypes correspond to epithelioid and fibroblastoid subsets, respectively. Both sorted subsets displayed different levels of tumorigenicity in xenotransplantation, indicating that each harbored its own cancer stem cells (CSCs). The CD44bright/CD24bright subset, associated with higher expression of MMP-7, -8 and TIMP-1 transcripts, showed greater migratory/invasive potential than the CD44bright/CD24dim subset, which was associated with higher expression of MMP-2, -9 and TIMP-2 transcripts. Both subsets differentially expressed stemness gene products c-Myc, Oct4A, Notch1, Notch2 and Notch3, and the RCC stem cell marker, CD105 in 4-5% of RCC52 cells. These results suggest the presence of CSCs in both sRCC subsets for the first time and should therefore be considered potential therapeutic targets for this aggressive malignancy.
doi:10.18632/oncotarget.14777
PMCID: PMC5362508  PMID: 28121626
cancer stem cells; sarcomatoid renal cell carcinoma; epithelioid and fibroblastoid subsets; CD24; CD44
12.  Abstracts from the 8th International Congress of the Asia Pacific Society of Infection Control (APSIC) 
Sutthiruk, Nantanit | Botti, Mari | Considine, Julie | Driscoll, Andrea | Hutchinson, Ana | Malathum, Kumthorn | Cucunawangsih, Cucunawangsih | Wiwing, Veronica | Puspitasari, Vivien | Shanmugakani, Rathina Kumar | Akeda, Yukihiro | Kodera, Takuya | Santanirand, Pitak | Tomono, Kazunori | Yamanaka, Takayuki | Moriuchi, Hiroyuki | Kitajima, Hiroyuki | Horikoshi, Yuho | Lavrinenko, Alyona | Azizov, Ilya | Tabriz, Nurlan | Kozhamuratov, Margulan | Serbo, Yekatherine | Yang, Dahae | Lee, Woonhyoung | Bae, Il Kwon | Lee, Jae Hyun | Lee, Hyukmin | Kim, Jung Ok | Jeong, Seok Hoon | Lee, Kyungwon | Peremalo, Thiba | Madhavan, Priya | Hamzah, Sharina | Than, Leslie | Wong, Eng Hwa | Desa, Mohd Nasir Mohd | Ng, Kee Peng | Geronimo, Marionne | Tayzon, Maria Fe | Maño, Maria Jesusa | Chow, Angela | Hon, Pei-Yun | Win, Mar-Kyaw | Ang, Brenda | Leo, Yee-Sin | Chow, Angela | Hon, Pei-Yun | See, Tina | Ang, Brenda | Marin, Rocio Alvarez | de Sousa, Marta Aires | Kieffer, Nicolas | Nordmann, Patrice | Poirel, Laurent | Laochareonsuk, Wison | Petyu, Sireekul | Wanasitchaiwat, Pawin | Thana, Sutasinee | Bunyaphongphan, Chollathip | Boonsomsuk, Woranan | Maneepongpermpoon, Pakpoom | Jamulitrat, Silom | Sureshkumar, Dorairajan | Supraja, Kalyanaraman | Sharmila, Soundararajan | Cucunawangsih, Cucunawangsih | Setiawan, Benny | Lumbuun, Nicolaski | Nakayama, Haruo | Ota, Toshiko | Shirane, Naoko | Matuoka, Chikako | Kodama, Kentaro | Ohtsuka, Masanobu | Bacolcol, Silverose Ann Andales | Velmonte, Melecia | Alde, Allan | Chavez, Keithleen | Esteban, Arlene Joy | Lee, Aisa Jensen | Hsieh, Tai-Chin | Shio-ShinJean | Huang, Huey-Jen | Huang, Shu-Ju | Huang, Yu-Huan | Cheng, Pei-Chen | Yu, Su-Fang | Tsao, Shih-Ming | Lee, Yuan-Ti | Li, Chien-Feng | Lu, Min-Chi | Pruetpongpun, Nattapol | Khawcharoenporn, Thana | Damronglerd, Pansachee | Suwantarat, Nuntra | Apisarnthanarak, Anucha | Rutjanawech, Sasinuch | Cushinotto, Lisa | McBride, Patty | Williams, Harding | Liu, Hans | Hang, Phan Thi | Anh, Dinh Pham Phuong | Le, Ngai | Khu, Dung | Nguyen, Lam | Castillo, Roel Beltran | Sureshkumar, Dorairajan | Gopalakrishnan, Ram | Ramasubramanian, Venkatasubramanian | Sreevidya, Subramanian | Jayapradha, Ranganathan | Umetsu, Atsushi | Noda, Tetsuhiro | Hashimoto, Kenyuu | Hayashi, Akihiro | Kabashima, Mikie | Jadczak, Ursula | Elvelund, Knut | Johnsen, Marit | Borgen, Bente | Lingaas, Egil | Mao, Chia-Hua | Chang, Fu-Chieh | Liu, Chang-Pan | Chao, Ru-Hui | Chang, Fu-chieh | Liu, Chang-pan | Pawapotako, Junpen | Prasertpan, Chadanan | Malaihuan, Wantanee | Uirungroj, Phisit | Prasertpan, Chadanan | Saenjum, Chalermpong | Ouirungrog, Teerapat | Uirungroj, Phisit | Borrell, Sue | Bass, Pauline | Worth, Leon | Xian-li, Zhao | Xiao-long, Li | Xue-hua, Yao | Wei, Ren | Zeng, Zhang Xia | Kong, Man Ying | Lai, Christopher Koon Chi | Lee, Suet Yi | Tsang, Ngai Chong | O’Donoghue, M. M. | Boost, M. V. | Suen, L. K. P. | Siu, G. K. | Mui, K. W. | Lai, C. K. C. | Tsang, D. N. C. | Sato, Yuka | Tateishi, Mariko | Mihashi, Mutsuko | Flor, Jose Paulo | Bautista, Marko | De Roxas, V. Jay | Vergara, Justine | Añonuevo, Nicolo Andrei | Kwek, Marion | Acuin, Jose | Sanchez, Anna Josea | Bathan, Avel | Jantan, Jamilah Binte | Guek, Chua Chor | Kian, Eu Chiow | Pirido, Pampe Anak | Aron, Nur Fadilah Binte Mohd | Estacio, Leah May | Palana, Francis Alvarez | Gracia, Michelle | Shamsuddin, Nur Syafiqah Binte | Castro, Kersten Timbad | Baloria, Madonna | Adam, Faezah Binte | Wei, Zhang | Fong, Poh Bee | Kalisvar, Marimuthu | Chow, Angela | Ang, Brenda | Chuang, I-Ju | Yi-ChunCho | Chiu, Yu-Fen | Chen, Lung-Chih | Lin, Yi-Chun | Dong, Shao-Xing | Lee, Yi-Chieh | Kuan, Hui-Chen | Lin, Hsin-Hua | Chi, Chia-Chun | Lu, Chin-Te | Chang, Fu-chieh | Liu, Chang-pan | Ya-Fen, Tang | Li-Hsiang, Su | Jien-Wei, Liu | Chao, Hsuehlan | ChangChien, PinRu | Chen, WeiFang | Lai, ChungHsu | Ara, Lutfe | Mowla, Syed Mohammad Niaz | Vashkar, Shaikh Mahmud Kamal | Chan, Wai Fong | ChunYau, Mabel Yin | LingChong, Karen Kam | OnLi, Tze | Kaur, Rajwinder | Yan, Ng Po | Chiu, Gloria Chor Shan | Cheung, Christina W. Y. | Ching, Patricia T. Y. | Ching, Radley H. C. | Lam, Conita H. S. | Kan, C. H. | Lee, Shirley S. Y. | Chen, C. P. | Chan, Regina F. Y. | Leung, Annie F. Y. | Wong, Isadora L. C. | Lam, S. S. | Chan, Queenie W. L. | Chan, Cecilia | Kaur, Rajwinder | Nematian, Seyed Sadeq Seyed | Palenik, Charles John | Askarian, Mehrdad | Nematian, Seyed Sadeq Seyed | Palenik, Charles John | Hatam, Nahid | Askarian, Mehrdad | Nakamura, Itaru | Fujita, Hiroaki | Tsukimori, Ayaka | Kobayashi, Takehito | Sato, Akihiro | Fukushima, Shinji | Matsumoto, Tetsuya | Flor, Jose Paulo | Añonuevo, Nicolo Andrei | Bautista, Marko | Vergara, Justine | De Roxas, V. James | Kwek, Marion | Flor, Jose Paulo | Bautista, Marko | Vergara, Justine | De Roxas, V James | AndreiAñonuevo, Nicolo | Kwek, Marion | Ho, Yeng May | Kum, Jia Qi | Poh, Bee Fong | Marimuthu, Kalisvar | Ang, Brenda | Liu, Tzu-Yin | Chu, Sin-Man | Chen, Hui-Zhu | Chen, Tun-chieh | Chen, Yichun | Tsao, Ya-Ching | Skuntaniyom, Sumawadee | Malathum, Kumthorn | Tipluy, Pirawadee | Paengta, Sangwan | wongsaen, Ratchanee | thanomphan, Sutthiphun | Tariyo, Samettanet | Thongchuea, Buachan | Khamfu, Pattama | Thanomphan, Sutthiphan | Songtaweesin, Wipaporn Natalie | Anugulruengkit, Suvaporn | Samransamruajkit, Rujipat | Sosothikul, Darintr | Tansrijitdee, Ornanong | Nakphunsung, Anry | Srimuan, Patchareeyawan | Sophonphan, Jirachaya | ThanyaweePuthanakit | Payuk, Kunyanut | Picheansathian, Wilawan | Viseskul, Nongkran | DeNardo, Elizabeth | Leslie, Rachel | Cartner, Todd | Barbosa, Luciana | Werner, Heinz-Peter | Brill, Florian H. H. | Kawagoe, Julia Yaeko | De Nardo, Elizabeth | Wilson, Sarah Edmonds- | Macinga, David | Mays-Suko, Patricia | Duley, Collette | Hang, Phan Thi | Hang, Tran Thi Thuy | Hanh, Tran Thi My | Gordon, Christopher | Sureshkumar, Dorairajan | Durairaj, Roopa | Rohit, Anusha | Saravanakumar, Saujanya | Hemalatha, Jothymani | Hirano, Ryuichi | Sakamoto, Yuichi | Yamamoto, Shoji | Tachibana, Naoki | Miura, Miho | Hieda, Fumiyo | Sakai, Yoshiro | Watanabe, Hiroshi | Velmonte, Melecia | Bacolcol, Silverose Ann | Alde, Allan | Chavez, Keitleen | Esteban, Arlene Joy | Lee, Aisa Jensen | Chow, Angela | Lim, Jia-Wei | Hon, Pei-Yun | Hein, Aung-Aung | Tin, Grace | Lim, Vanessa | Ang, Brenda | Chow, Angela | Hein, Aung-Aung | Lim, Jia-Wei | Hon, Pei-Yun | Lim, Vanessa | Tin, Grace | Ang, Brenda | Chow, Angela | Tin, Grace | Hein, Aung-Aung | Lim, Vanessa | Lim, Jia-Wei | Hon, Pei-Yun | Ang, Brenda | Chao, Huwi-chun | Yeh, Chiu-Yin | Lo, Mei-feng | Chao, Huwi-chun | Piwpong, Chonlada | Rajborirug, Songyos | Preechawetchakul, Ploypailin | Pruekrattananapa, Yada | Sangsuwan, Tharntip | Jamulitrat, Silom | Wongsaen, Ratchanee | Paengta, Sungwan | Nilchon, Napatnun | Thanompan, Sutthipun | Tariyo, Samattanet | Le, Ngai | Khu, Dung | Kolesnichenko, Svetlana | Azizov, Ilya | Lavrinenko, Alyona | Tishkambayev, Yerbol | Lavrinenko, Alyona | Azizov, Ilya | Tishkambayev, Yerbol | Alibecov, Asylkhan | Kolesnichenko, Svetlana | Serbo, Yekaterina | Nam, Youngwon | Park, Jae Hyeon | Hong, Yun Ji | Kim, Taek Soo | Park, Jeong Su | Park, Kyoung Un | Kim, Eui-Chong | Aziegbemhin, Samuel Abumhere | Enabulele, Onaiwu | Tung, Yao-Shen | Chen, An-Chi | Huang, Shen-Min | Yang, Yui-Yein | Wu, Li-Hung | Lin, Chin-cheng | Chang, Fu-chieh | Liu, Chang-pan | Lien, Tzu Hao | Chang, Jia Hao | Huang, Yu Shan | Chen, Yi Shun | Saenjum, Chalermpong | Sirilun, Sasithorn | Ouirungrog, Teerapat | Ouirungroj, Phisit | Trakulsomboon, Suwanna | Prasajak, Patcharee | Kwok, Maryanne W. N. | Ng, Lady S. H. | Wong, Lindy M. T. | Poon, Lenina S. L. | Lai, Mary K. L. | Cheng, Holly H. S. | Fong, S. K. | Leung, Cindy F. Y. | Hasegawa, Jumpei | Shirakawa, Hiroki | Wakai, Sachiko | Mieno, Makiko | Hatakeyama, Shuji | Tateishi, Mariko | Mihashi, Mutsuko | Sato, Yuka | Saenjum, Chalermpong | Deeudom, Manu | Tharavichitkul, Prasit | Ouirungrog, Teerapat | Ouirungroj, Phisit | Chinniah, Terrence | Tan, Jackson | Prabu, Kavitha | Alam, Sartaj | Wynn, Aung Kyaw | Ahmad, Rashidah | Sidek, Amalina | Samsuddin, Dg Azizah | Ajis, Noraini | Ahmad, Aliyah | Magon, Susylawathi | Chu, Boon | Kuang, Jiqiu | Gao, Yan | Wang, Shoujun | Hao, Yunxiao | Liu, Rong | Li, Dongmei | Wang, Hui | Yan, Ng Po | Nishio, Hisanori | Mori, Hitomi | Morokuma, Yoshiko | Yamada, Takaaki | Kiyosuke, Makiko | Yasunaga, Sachie | Toyoda, Kazuhiro | Shimono, Nobuyuki | Babenko, Dmitriy | Turmuhambetova, Anar | Cheşcă, Antonella | Toleman, Mark A. | Babenko, Dmitriy | Turmuhambetova, Anar | Cheşcă, Antonella | Toleman, Mark A. | Babenko, Dmitriy | Turmuhambetova, Anar | Azizov, Ilya | Cheşcă, Antonella | Toleman, Mark A. | Akhmaltdinova, Lyudmila L. | Turmuhambetova, Anar | Cheşcă, Antonella | Babenko, Dmitriy | Magsakay, Mark Albert | Macatibag, Angelo | Tayzon, Maria Fe | Lerios, Jeannica Kriselle | Azizov, Ilya | Lavrineko, Alyona | Babenko, Dmitry | Sheck, Eugene | Edelstein, Mikhail | Liu, Tzu-Yin | Li, Lih-Yue | Chan, Chiung-Wen | Pan, Hui-Chuan | Chen, Tun-chieh | Vanishakije, Wipa | Jaikampun, Warisra | Cheng, Pei-Chen | Huang, Huey-Jen | Huang, Shu-Ju | Huang, Yu-Huan | Li, Su-Yin | Yu, Su-Fang | Li, Jian-Feng | Wu, Yu-Ping | Lee, Yuan-Ti | Lin, Chiao-Hui | Chang, Ping-Chin | Tariyo, Samatanet | Paengta, Sangwan | Wongsaen, Ratchanee | Thanompan, Suttsiphan | Skuntaniyom, Sumawadee | Malathum, Kumthorn | Sukkra, Suchada | Zaman, Khalequ | Zaman, Sheikh Farzana | Zaman, Farzana | Aziz, Asma | Faisal, Sayeed-Bin | Traskine, Magali | Ruiz-Guiñazú, Javier | Borys, Dorota | Zaman, Khalequ | Zaman, Sheikh Farzana | Zaman, Farzana | Aziz, Asma | Faisal, Sayeed-Bin | Traskine, Magali | Ruiz-Guiñazú, Javier | Borys, Dorota | Lam, Wendy Wai Yee | Chow, May | Choy, Lucy | Kam, Joseph | Salleh, Sharifah Azura | Yacob, Razila | Yusof, Siti Rokiah | Jalil, Nordiah Awang | Flor, Jose Paulo | Añonuevo, Nicolo Andrei | Bautista, Marko | De Roxas, V. Jay | Vergara, Justine | Millan, Maria Lourdes | Kwek, Marion | Acuin, Jose Lito | Lee, Aisa Jensen | Velmonte, Melecia A. | Bacolcol, Silverose Ann A. | Alde, Allan | Chavez, Keitleen | Esteban, Arlene Joy | Ting, Ching-I | Dissayasriroj, Sunisa | Chinniah, Terrence Rohan | Prabu, Kavitha | Ahmad, Rashidah | Magon, Susylawathi | DiniSuhaimi, Jauharatud | Mirasin, Aizzuddin | Morni, Nurul | Chu, Boon | Samsuddin, Azizah | Ahmad, Aliyah | Sidek, Amalina | Ajis, Noraini | AbuBakar, Amalina | Shafiee, Amanie | Safar, Julaini | Yan, Ng Po | Annie, Leung | Ling, Fung Yuk | Edna, Lau | Kristine, Luk | Shinomiya, Satoshi | Yamamoto, Kumiko | Kjiwara, Kayoko | Yamaguchi, Mitsuhiro | Chow, Angela | Tin, Grace | Zhang, Wei | Hon, Pei-Yun | Poh, Bee-Fong | Marimuthu, Kalisvar | Ang, Brenda | Chan, Ming-Chin | Wang, Chih-Chien | Huang, Shu-Ju | Huang, Huey-Jen | Yu, Su-Fang | Huang, Huan-Yu | Cheng, Pei-Chen | Li, Jian-Feng | Lee, Yuan-Ti | Lai, Chiung-Ling | Lu, Min-Chi | Kosol, Sajeerat | Sakolwirat, Wantana | Paepong, Patchanee | Jansanga, Sawalee | Jaisamoot, Pattarin | Thongnuanual, Nuttha | Srithong, Chittima | Somsakul, Somporn | Malathum, Kumthorn | Plongpunth, Sutima | Punpop, Mukkapon | Malathum, Porntip | Malathum, Kumthorn | Thanomphan, Sutthiphan | Wongsaen, Ratchanee | Peautiwat, Kulada | boon kirdram, Nattawipa | Picheansathian, Wilawan | Klunklin, Pimpaporn | Samethadka, Geetha | Suzuki, Naoko | Asada, Hitomi | Katayama, Masao | Komano, Atsushi | Sato, Akihiro | Nakamura, Itaru | Watanabe, Hidehiro | Matsumoto, Tetsuya | Seo, Hye Kyung | Hwang, Joo-Hee | Shin, Myoung Jin | Kim, Su Young | Kim, Eu Suk | Song, Kyoung-Ho | Kim, Hong Bin | Un, Lai-Si | Vong, Choi-Ian | Flor, Jose Paulo | Añonuevo, Nicolo Andrei | Bautista, Marko | De Roxas, V. James | Vergara, Justine | Kwek, Marion | Koh, Jocelyn | Agustinus, Sherly | Hassan, Rozita Bte Abu | Thinn, Yin Phyu | Ng, Benjamin | Tun, Soe Pyae | Ha, Su Mon Thi | Xiaoting, Xue | Li, Lin | Chuang, Leyland | Niroshika, Attanayaka Mudiyanselage Chulani | Perera, Kaluarachchige Anoma Kaluarachchi | Fernando, Dimingo Kankanamalage Diana Grace | Hemamala, Bodhipakshage Rohini | Yeh, Chiu-yin | Chao, Huwi-chun | Yang, Hui-Chun | Chiu, Hsiang-Ju | Shih, Ya-Ling | Chien, Yu-Shan | Lin, Wan-Yi | Pan, Chia-Yun | Chang, Ying-Yun | Yea, Chiu-Yuch | Chu, Ming-Hsien | Lee, Li-Chu | Chiu, Hsiang-Ju | Shih, Ya-Ling | Yang, Hui-Chun | Yu-Hsiu, Lin | Siao-Pei, Guo | Pak-On, Leung | Mei-Fe, Sie | Jyh-Jou, Chen | Yu-Hsiu, Lin | Yong-Yuan, Chang | Kuo, Shu-Yuan | Lin, Yu-Hsiu | Zhang, Ji-Sheng | Leung, Pak-On | Sie, Mei-Fe | Chen, Jyh-Jou | Chen, Yan-Ru | Lin, Yu-Hsiu | Chen, Ying-Ling | Taou, Chi-Fen | Chen, Hsiao-Shan | Tang, Hung-Jen | Chen, Shin Yu | Chen, Yin Yin | Der Wang, Fu | Shih, Tzu-Ping | Chen, Chin-Yu | Chen, Su-Jung | Wu, Mei-chi | Yang, Wan-ju | Chou, Mei-ling | Yu, Man-Ling | Li, Li-Chu | Chu, Cheng-Wei | Tsou, Wen-Hao | Wu, Wen-Chih | Cheng, Wen-Chi | Sun, Cho-Ching | Shih, Tzu-Ping | Chen, Chin-Yu | Lu, Shu-Hua | Chen, Su-Jung | Yang, Hsin-Ling | Lu, Cheng-Yu | Yu, Man-Ling | Li, Li-Chu | Chu, Cheng-Wei | Tsou, Wen-Hao | Wu, Wen-Chih | Cheng, Wen-Chi | Sun, Cho-Ching | Hirunprapakorn, Nitchawan | Malathum, Kumthorn | Apivanich, Sirilux | Pornmee, Ttipakorn | Beowsomboon, Chonnikarnt | Rajborirug, Songyos | Pruekrattananapa, Yada | Sangsuwan, Tharntip | Jamulitrat, Silom | Kumkoom, Itthaporn | Kasatpibal, Nongyao | Chitreecheur, Jittaporn | Kasatpibal, Nongyao | Whitney, JoAnne D. | Saokaew, Surasak | Kengkla, Kirati | Heitkemper, Margaret M. | Apisarnthanarak, Anucha | Muntajit, Thanomvong | Apivanich, Siriluk | Malathum, Kumthorn | Somsakul, Somporn | Phan, Hang Thi | Dinh, Anh Pham Phuong | Nguyen, Tuyet Thi Kim
doi:10.1186/s13756-017-0176-1
PMCID: PMC5333188
13.  A comparison between angiotensin converting enzyme inhibitors and angiotensin receptor blockers on end stage renal disease and major adverse cardiovascular events in diabetic patients: a population-based dynamic cohort study in Taiwan 
Background
Contemporary guidelines recommend angiotensin-converting-enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARB) for hypertensive patients with diabetes. However, there is limited data to evaluate the comparison between ACEi and ARB on end stage renal disease (ESRD) and major adverse cardiovascular events (MACE), in Asian diabetic patients.
Methods
We used the Taiwan Longitudinal Cohort of Diabetes Patients Database to perform a population-based dynamic cohort study. The comparison between ACEi and ARB on ESRD and MACE in diabetic patients was examined using the propensity score weighting method. We followed these patients until the occurrence of first study outcomes or end date of the study, whichever came first.
Results
There were 6898 and 12,758 patients in ACEi and ARB groups, respectively. The mean follow-up period was about 3.5 years in ESRD and 2.5 years in MACE. The incidence of ESRD was 0.44 % and 0.63 % per person-years in the ACEi and ARB group, respectively. The risk of ESRD was lower in the ACEi group than the ARB group [hazard ratio (HR) 0.69; 95 % confidence interval (CI) 0.54–0.88, P = 0.0025]. Among those without chronic kidney disease (CKD), the incidence of ESRD was 0.30 % and 0.37 % per person-years in the ACEi and ARB group, respectively. ACEi was similar to ARB in preventing ESRD for those without CKD (P = 0.11). Among those with CKD, the incidence of ESRD was 1.39 % and 2.34 % per person-years in the ACEi and ARB group, respectively. The ACEi group had a lower risk of ESRD than the ARB group (HR 0.61; 95 % CI 0.42–0.88, P = 0.008). The incidence of MACE was 9.33 % and 9.62 % per person-years in the ACEi and ARB group, respectively. There was no significant difference in the composite MACE outcome between the two groups (P = 0.42), but the ACEi group was associated with a higher risk of stroke than the ARB group (HR 1.12; 95 % CI 1.02–1.24, P = 0.02).
Conclusions
ACEi compared with ARB was associated with a lower incidence of ESRD, especially in those with CKD. Though ACEi and ARB had a similar risk of composite MACE outcome, ACEi had a slightly higher incidence of stroke than ARB, among the Asian diabetic patients.
Electronic supplementary material
The online version of this article (doi:10.1186/s12933-016-0365-x) contains supplementary material, which is available to authorized users.
doi:10.1186/s12933-016-0365-x
PMCID: PMC4818874  PMID: 27039185
Angiotensin converting enzyme inhibitors; Angiotensin receptor blockers; Diabetes mellitus; Major adverse cardiovascular events; End-stage renal disease
14.  Young Male Patients with Atrial Fibrillation and CHA2DS2-VASc Score of 1 May Not Need Anticoagulants: A Nationwide Population-Based Study 
PLoS ONE  2016;11(3):e0151485.
Background
It is unclear whether oral anticoagulants are beneficial for atrial fibrillation (AF) patients with low CHA2DS2-VASc score. Age could be important in determining the risk of thromboembolism in low risk AF patients (CHA2DS2-VASc score of 1 for male or 2 for female).
Methods
The Taiwan National Health Insurance Research Database (NHIRD) was used and 27,521 AF patients with CHA2DS2-VASc score of 1 (male) or 2 (female) not receiving anticoagulants were acquired as the study cohort, which were classified into three age groups: 20–49, 50–64, and 65–74 years. The clinical endpoint was the occurrence of ischemic thromboembolism within one year of follow up.
Results
During the follow-up of 0.94 ± 0.19 years, 385 (2.19%) male patients experienced ischemic thromboembolism, with annual rate of 2.32%. The annual risk ranged from 1.29%, 2.43% to 2.77% for male patients aged 20–49, 50–64 and 65–74 years respectively. Of the female patients, 218 (2.20%) experienced clinical event with annual rate of 2.32%. The annual risk increased from 1.87%, 2.28% to 2.64% for female patients aged 20–49, 50–64 and 65–74 years respectively. There was no difference in risk between the male patients aged 20–49 years with CHA2DS2-VASc score of 1 and overall male patients with CHA2DS2-VASc score of 0. (P = 0.631) The female patients aged 20–49 years with CHA2DS2-VASc score of 2 was associated with a higher risk of thromboembolic events than overall female patients with CHA2DS2-VASc score of 1 (HR = 1.93; P = 0.008).
Conclusions
Age is important in determining the risk of thromboembolism in AF patients with single risk factor. In male patients <50 years old with CHA2DS2-VASc score of 1, the risk of ischemic thromboembolism was low. Considering the benefits and the risk of bleeding, oral anticoagulation therapy may not be favorable in these patients.
doi:10.1371/journal.pone.0151485
PMCID: PMC4795759  PMID: 26986069
15.  Dialysis Patients with Implanted Drug-Eluting Stents Have Lower Major Cardiac Events and Mortality than Those with Implanted Bare-Metal Stents: A Taiwanese Nationwide Cohort Study 
PLoS ONE  2016;11(1):e0146343.
Objective
To investigate the efficacy and long-term clinical benefits of DES for dialysis patients.
Background
It is unclear whether percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation is associated with lower rates of major adverse cardiovascular events (MACE) or mortality compared to bare-metal stents (BMS).
Methods
From a nationwide cohort selected from Taiwan’s National Health Insurance Research Database, we enrolled 2,835 dialysis patients who were hospitalized for PCI treatment with stent implantation from Dec 1, 2006. Follow-up was from the date of index hospitalization for PCI until the first MACE, date of death, or December 31, 2011, whichever came first.
Results
A total of 738 patients (26.0%) had DES implanted, and 2,097 (74%) had BMS implanted. The medium time to the first MACE was 0.53 years (interquartile range: 0.89 years; range: 0–4.62 years). At 1-year follow-up, patients treated with BMS had significantly, non-fatal myocardial infarction (MI), all-cause mortality, and composite MACE compared to those treated with DES. The overall repeat revascularization with coronary artery bypass graft (CABG), non-fatal MI, all-cause mortality, and composite MACE were significantly lower in patients treated with DES than those treated with BMS. Multivariate cox regression analysis showed that older age, history of diabetes, history of heart failure, history of stroke, and DES vs. BMS were independent significant predictors of MACE.
Conclusions
DES implantation conferred survival benefits in dialysis patients compared with BMS implantation.
doi:10.1371/journal.pone.0146343
PMCID: PMC4711720  PMID: 26731408
16.  Delayed presentation of compartment syndrome of the thigh secondary to quadriceps trauma and vascular injury in a soccer athlete 
Highlights
•Our case the difficulty of differentiating severe quadriceps contusion from thigh compartment syndrome.•We ed the response of thigh musculature to blunt trauma.•Clinicians should be aware of vascular injury as a cause of thigh compartment syndrome in sports trauma. Vascular examination is warranted in all cases of quadriceps injury.•MRI findings of deep thigh muscle swelling and “blow-out” tear of the vastus lateralis are strongly suggestive of severe quadriceps injury, and may be a harbinger of delayed thigh compartment syndrome.
Introduction
Compartment syndrome isolated to the anterior thigh is a rare complication of soccer injury. Previous reports in the English literature on sports trauma-related compartment syndrome of the thigh are vague in their description of the response of thigh musculature to blunt trauma, magnetic resonance imaging (MRI) findings of high-risk features of compartment syndrome, vascular injury in quadriceps trauma, and the role of vascular study in blunt thigh injury.
Case report
We present herein the rare case of a 30-year-old man who developed thigh compartment syndrome 8 days after soccer injury due to severe edema of vastus intermedius and large thigh hematoma secondary to rupture of the profunda femoris vein. MRI revealed “blow-out” rupture of the vastus lateralis. Decompressive fasciotomy and vein repair performed with subsequent split-skin grafting of the wound defect resulted in a good functional outcome at 2-years follow-up.
Conclusion
A high index of suspicion for compartment syndrome is needed in all severe quadriceps contusion. Vascular injury can cause thigh compartment syndrome in sports trauma. MRI findings of deep thigh muscle swelling and “blow-out” tear of the vastus lateralis are strongly suggestive of severe quadriceps injury, and may be a harbinger of delayed thigh compartment syndrome.
doi:10.1016/j.ijscr.2015.04.003
PMCID: PMC4446675  PMID: 25931302
Quadriceps injury; Acute compartment syndrome; Fasciotomy; Soccer
17.  Risk Factors for Hospital and Long-Term Mortality of Critically Ill Elderly Patients Admitted to an Intensive Care Unit 
BioMed Research International  2014;2014:960575.
Background. Data on long-term outcomes of elderly (≥65 years) patients in ICU are sparse. Materials and Methods. Adult patients (n = 1563, 45.4% elderly) admitted over 28 months were analyzed by competing risks regression model to determine independent factors related to in-hospital and long-term mortality. Results. 414 (26.5%) and 337 (21.6%) patients died in-hospital and during the 52 months following discharge, respectively; the elderly group had higher mortality during both periods. After discharge, elderly patients had 2.3 times higher mortality compared to the general population of the same age-group. In-hospital mortality was independently associated with mechanical ventilation (subdistribution hazard ratio (SHR) 2.74), vasopressors (SHR 2.56), neurological disease (SHR 1.77), and Mortality Prediction Model II score (SHR 1.01) regardless of age and with malignancy (SHR, hematological 3.65, nonhematological 3.4) and prior renal replacement therapy (RRT, SHR 2.21) only in the elderly. Long-term mortality was associated with low hemoglobin concentration (SHR 0.94), airway disease (SHR 2.23), and malignancy (SHR hematological 1.11, nonhematological 2.31) regardless of age and with comorbidities especially among the nonelderly. Conclusions. Following discharge, elderly ICU patients have higher mortality compared to the nonelderly and general population. In the elderly group, prior RRT and malignancy contribute additionally to in-hospital mortality risk. In the long-term, comorbidities (age-related), anemia, airway disease, and malignancy were significantly associated with mortality.
doi:10.1155/2014/960575
PMCID: PMC4280808  PMID: 25580439
18.  Profiling of matrix metalloproteinases and tissue inhibitors of metalloproteinases proteins in bladder urothelial carcinoma 
Oncology Letters  2010;1(4):691-695.
We investigated the matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) proteins in transitional cell carcinoma (TCC) cell lines and surgical specimens of the bladder neoplasm. The expression level was correlated to the degree of cellular differentiation and invasiveness of bladder cancer. Panels of six TCC cell lines with different degrees of differentiation were tested with monoclonal antibodies (mAbs) to MMP-1, MMP-2, MMP-3, MMP-9a, MMP-9b, TIMP-1 and TIMP-2 by immunocytochemistry. Gelatin zymography was also conducted on the cell lines for MMP-2 and -9. In addition, immunohistochemistry with the mAbs to MMP and TIM molecules was performed on 30 TCC specimens. We found that TCC cell lines were stained positively for MMP-1 (6/6), weakly for MMP-9a (2/6), MMP9b (5/6) and TIMP-1 (3/6), and negatively for MMP-2 (3/6) and MMP-3 (3/6). Zymographic analysis of the cell lines showed a high level of MMP2 in the MGH-U4 cell line. In bladder cancer surgical specimens, all specimens were positive for MMP1 (30/30), 19 were positive for MMP-2 (63.3%), 21 positive for MMP-9a (70%) and 15 positive for MMP-9b (50%). The expression of MMP-2 was found to be positively correlated with higher-grade tumors (p=0.036) and the expression of MMP-9a and -9b was found to be positively correlated with tumor stage (p=0.012 and 0.023, respectively). However, the expression of MMP-1, MMP-3, TIMP-1 and TIMP-2 was not correlated with either tumor staging or grading. In conclusion, the expression of MMP-2 and -9 was correlated with high-grade or high-stage bladder tumors, respectively. However, this correlation was not observed with TCC cell lines in which high- and low-grade tumors are included. Immunohistochemical results on tumor lesions may have more clinical relevance, since in a given tumor microenvironment the interaction among tumor cells in situ and tumor-associated cells, such as neutrophils, macrophages, lymphocytes and endothelial cells, as well as environmental factors (hypoxia and pH), cytokines and growth factors released by these cells may be required for TCC to express selective MMPs and TIMPs. The selective expression of these molecules then regulates tumor progression.
doi:10.3892/ol_00000121
PMCID: PMC3436408  PMID: 22966365
bladder neoplasm; metastasis; matrix metalloproteinases; cell line; tissue inhibitors of metalloproteinases
19.  Deep neck abscess: an analysis of microbial etiology and the effectiveness of antibiotics 
The objective was to demonstrate the aerobic and anaerobic microbiology of deep neck space abscess and to analyze the coverage rate of different empiric antimicrobial agents. A retrospective review of hospitalized patients with deep neck abscess diagnosed at a tertiary-care, general hospital between April 2001 and October 2006. The study enrolled 100 patients. The bacterial cultures of 89 patients yielded positive results (89%). The predominant aerobes were viridans streptococci, Klebsiella pneumoniae, and Staphylococcus aureus. The predominant anaerobes included species of Prevotella, Peptostreptococcus, and Bacteroides. Five different combinations of empiric antibiotics, namely regimen 1: penicillin G and clindamycin and gentamicin, regimen 2: ceftriaxone and clindamycin, regimen 3: ceftriaxone and metronidazole, regimen 4: cefuroxime and clindamycin, and regimen 5: penicillin and metronidazole, were compared using the antimicrobial susceptibility of 89 cases. The coverage rates of regimens 1, 2, 3, 4, and 5 were 67.4%, 76.4%, 70.8%, 61.8%, and 16.9%, respectively. The coverage of regimen 5 was considerably worse than that of the other four regimens (p < 0.001). Regimen 2 was significantly better than regimen 4 (p < 0.001). Regimen 2 had better coverage than regimens 1 (p = 0.096) and 3 (p = 0.302), but the difference was not statistically significant. This study demonstrates the bacteriology of deep neck abscess and analyzes the coverage rate of different empiric antimicrobial agents. Regimens 1, 2, and 3 could be good candidates for empiric antibiotics. Pathogen-directed antimicrobial therapy should be adjusted after the culture results are obtained.
PMCID: PMC3108716  PMID: 21694873
deep neck abscess; microbiology; antibiotics; empiric
20.  Surgery and adjuvant radiotherapy vs concurrent chemoradiotherapy in stage III/IV nonmetastatic squamous cell head and neck cancer: a randomised comparison 
British Journal of Cancer  2005;93(3):279-286.
We compared concurrent combination chemotherapy and radiotherapy with surgery and adjuvant radiotherapy in patients with stage III/IV nonmetastatic squamous cell head and neck cancer. Patients with non-nasopharyngeal and nonsalivary resectable squamous cell head and neck cancer were randomised to receive either surgery followed by adjuvant radiotherapy (60 Gy over 30 fractions) or concurrent combination chemotherapy and radiotherapy (66 Gy in 33 fractions). Combination chemotherapy comprised two cycles of i.v. cisplatin 20 mg m− 2 day− 1 and i.v. 5-fluorouracil 1000 mg m− 2 day− 1, both to run over 96 h given on days 1 and 28 of the radiotherapy. A total of 119 patients were randomised. At a median follow-up of 6 years, there was no significant difference in the 3-year disease-free survival rate between the surgery and concurrent chemoradiotherapy (50 vs 40% respectively). The overall organ preservation rate or avoidance of surgery to primary site was 45%. Those with laryngeal/hypopharyngeal disease subsite had a higher organ-preservation rate than the rest (68 vs 30%). Combination chemotherapy and concurrent irradiation with salvage surgery was not superior to conventional surgery and postoperative radiotherapy for resectable advanced squamous cell head and neck cancer. However, this form of treatment schedule with a view to organ-preservation can be attempted especially for those with laryngeal/hypopharyngeal and possibly oropharyngeal disease subsites.
doi:10.1038/sj.bjc.6602696
PMCID: PMC2361563  PMID: 16012523
randomised; squamous cell head and neck cancer; chemotherapy
21.  Guidelines for the use and interpretation of assays for monitoring autophagy 
Klionsky, Daniel J. | Abdalla, Fabio C. | Abeliovich, Hagai | Abraham, Robert T. | Acevedo-Arozena, Abraham | Adeli, Khosrow | Agholme, Lotta | Agnello, Maria | Agostinis, Patrizia | Aguirre-Ghiso, Julio A. | Ahn, Hyung Jun | Ait-Mohamed, Ouardia | Ait-Si-Ali, Slimane | Akematsu, Takahiko | Akira, Shizuo | Al-Younes, Hesham M. | Al-Zeer, Munir A. | Albert, Matthew L. | Albin, Roger L. | Alegre-Abarrategui, Javier | Aleo, Maria Francesca | Alirezaei, Mehrdad | Almasan, Alexandru | Almonte-Becerril, Maylin | Amano, Atsuo | Amaravadi, Ravi K. | Amarnath, Shoba | Amer, Amal O. | Andrieu-Abadie, Nathalie | Anantharam, Vellareddy | Ann, David K. | Anoopkumar-Dukie, Shailendra | Aoki, Hiroshi | Apostolova, Nadezda | Arancia, Giuseppe | Aris, John P. | Asanuma, Katsuhiko | Asare, Nana Y.O. | Ashida, Hisashi | Askanas, Valerie | Askew, David S. | Auberger, Patrick | Baba, Misuzu | Backues, Steven K. | Baehrecke, Eric H. | Bahr, Ben A. | Bai, Xue-Yuan | Bailly, Yannick | Baiocchi, Robert | Baldini, Giulia | Balduini, Walter | Ballabio, Andrea | Bamber, Bruce A. | Bampton, Edward T.W. | Juhász, Gábor | Bartholomew, Clinton R. | Bassham, Diane C. | Bast, Robert C. | Batoko, Henri | Bay, Boon-Huat | Beau, Isabelle | Béchet, Daniel M. | Begley, Thomas J. | Behl, Christian | Behrends, Christian | Bekri, Soumeya | Bellaire, Bryan | Bendall, Linda J. | Benetti, Luca | Berliocchi, Laura | Bernardi, Henri | Bernassola, Francesca | Besteiro, Sébastien | Bhatia-Kissova, Ingrid | Bi, Xiaoning | Biard-Piechaczyk, Martine | Blum, Janice S. | Boise, Lawrence H. | Bonaldo, Paolo | Boone, David L. | Bornhauser, Beat C. | Bortoluci, Karina R. | Bossis, Ioannis | Bost, Frédéric | Bourquin, Jean-Pierre | Boya, Patricia | Boyer-Guittaut, Michaël | Bozhkov, Peter V. | Brady, Nathan R | Brancolini, Claudio | Brech, Andreas | Brenman, Jay E. | Brennand, Ana | Bresnick, Emery H. | Brest, Patrick | Bridges, Dave | Bristol, Molly L. | Brookes, Paul S. | Brown, Eric J. | Brumell, John H. | Brunetti-Pierri, Nicola | Brunk, Ulf T. | Bulman, Dennis E. | Bultman, Scott J. | Bultynck, Geert | Burbulla, Lena F. | Bursch, Wilfried | Butchar, Jonathan P. | Buzgariu, Wanda | Bydlowski, Sergio P. | Cadwell, Ken | Cahová, Monika | Cai, Dongsheng | Cai, Jiyang | Cai, Qian | Calabretta, Bruno | Calvo-Garrido, Javier | Camougrand, Nadine | Campanella, Michelangelo | Campos-Salinas, Jenny | Candi, Eleonora | Cao, Lizhi | Caplan, Allan B. | Carding, Simon R. | Cardoso, Sandra M. | Carew, Jennifer S. | Carlin, Cathleen R. | Carmignac, Virginie | Carneiro, Leticia A.M. | Carra, Serena | Caruso, Rosario A. | Casari, Giorgio | Casas, Caty | Castino, Roberta | Cebollero, Eduardo | Cecconi, Francesco | Celli, Jean | Chaachouay, Hassan | Chae, Han-Jung | Chai, Chee-Yin | Chan, David C. | Chan, Edmond Y. | Chang, Raymond Chuen-Chung | Che, Chi-Ming | Chen, Ching-Chow | Chen, Guang-Chao | Chen, Guo-Qiang | Chen, Min | Chen, Quan | Chen, Steve S.-L. | Chen, WenLi | Chen, Xi | Chen, Xiangmei | Chen, Xiequn | Chen, Ye-Guang | Chen, Yingyu | Chen, Yongqiang | Chen, Yu-Jen | Chen, Zhixiang | Cheng, Alan | Cheng, Christopher H.K. | Cheng, Yan | Cheong, Heesun | Cheong, Jae-Ho | Cherry, Sara | Chess-Williams, Russ | Cheung, Zelda H. | Chevet, Eric | Chiang, Hui-Ling | Chiarelli, Roberto | Chiba, Tomoki | Chin, Lih-Shen | Chiou, Shih-Hwa | Chisari, Francis V. | Cho, Chi Hin | Cho, Dong-Hyung | Choi, Augustine M.K. | Choi, DooSeok | Choi, Kyeong Sook | Choi, Mary E. | Chouaib, Salem | Choubey, Divaker | Choubey, Vinay | Chu, Charleen T. | Chuang, Tsung-Hsien | Chueh, Sheau-Huei | Chun, Taehoon | Chwae, Yong-Joon | Chye, Mee-Len | Ciarcia, Roberto | Ciriolo, Maria R. | Clague, Michael J. | Clark, Robert S.B. | Clarke, Peter G.H. | Clarke, Robert | Codogno, Patrice | Coller, Hilary A. | Colombo, María I. | Comincini, Sergio | Condello, Maria | Condorelli, Fabrizio | Cookson, Mark R. | Coombs, Graham H. | Coppens, Isabelle | Corbalan, Ramon | Cossart, Pascale | Costelli, Paola | Costes, Safia | Coto-Montes, Ana | Couve, Eduardo | Coxon, Fraser P. | Cregg, James M. | Crespo, José L. | Cronjé, Marianne J. | Cuervo, Ana Maria | Cullen, Joseph J. | Czaja, Mark J. | D'Amelio, Marcello | Darfeuille-Michaud, Arlette | Davids, Lester M. | Davies, Faith E. | De Felici, Massimo | de Groot, John F. | de Haan, Cornelis A.M. | De Martino, Luisa | De Milito, Angelo | De Tata, Vincenzo | Debnath, Jayanta | Degterev, Alexei | Dehay, Benjamin | Delbridge, Lea M.D. | Demarchi, Francesca | Deng, Yi Zhen | Dengjel, Jörn | Dent, Paul | Denton, Donna | Deretic, Vojo | Desai, Shyamal D. | Devenish, Rodney J. | Di Gioacchino, Mario | Di Paolo, Gilbert | Di Pietro, Chiara | Díaz-Araya, Guillermo | Díaz-Laviada, Inés | Diaz-Meco, Maria T. | Diaz-Nido, Javier | Dikic, Ivan | Dinesh-Kumar, Savithramma P. | Ding, Wen-Xing | Distelhorst, Clark W. | Diwan, Abhinav | Djavaheri-Mergny, Mojgan | Dokudovskaya, Svetlana | Dong, Zheng | Dorsey, Frank C. | Dosenko, Victor | Dowling, James J. | Doxsey, Stephen | Dreux, Marlène | Drew, Mark E. | Duan, Qiuhong | Duchosal, Michel A. | Duff, Karen E. | Dugail, Isabelle | Durbeej, Madeleine | Duszenko, Michael | Edelstein, Charles L. | Edinger, Aimee L. | Egea, Gustavo | Eichinger, Ludwig | Eissa, N. Tony | Ekmekcioglu, Suhendan | El-Deiry, Wafik S. | Elazar, Zvulun | Elgendy, Mohamed | Ellerby, Lisa M. | Eng, Kai Er | Engelbrecht, Anna-Mart | Engelender, Simone | Erenpreisa, Jekaterina | Escalante, Ricardo | Esclatine, Audrey | Eskelinen, Eeva-Liisa | Espert, Lucile | Espina, Virginia | Fan, Huizhou | Fan, Jia | Fan, Qi-Wen | Fan, Zhen | Fang, Shengyun | Fang, Yongqi | Fanto, Manolis | Fanzani, Alessandro | Farkas, Thomas | Farre, Jean-Claude | Faure, Mathias | Fechheimer, Marcus | Feng, Carl G. | Feng, Jian | Feng, Qili | Feng, Youji | Fésüs, László | Feuer, Ralph | Figueiredo-Pereira, Maria E. | Fimia, Gian Maria | Fingar, Diane C. | Finkbeiner, Steven | Finkel, Toren | Finley, Kim D. | Fiorito, Filomena | Fisher, Edward A. | Fisher, Paul B. | Flajolet, Marc | Florez-McClure, Maria L. | Florio, Salvatore | Fon, Edward A. | Fornai, Francesco | Fortunato, Franco | Fotedar, Rati | Fowler, Daniel H. | Fox, Howard S. | Franco, Rodrigo | Frankel, Lisa B. | Fransen, Marc | Fuentes, José M. | Fueyo, Juan | Fujii, Jun | Fujisaki, Kozo | Fujita, Eriko | Fukuda, Mitsunori | Furukawa, Ruth H. | Gaestel, Matthias | Gailly, Philippe | Gajewska, Malgorzata | Galliot, Brigitte | Galy, Vincent | Ganesh, Subramaniam | Ganetzky, Barry | Ganley, Ian G. | Gao, Fen-Biao | Gao, George F. | Gao, Jinming | Garcia, Lorena | Garcia-Manero, Guillermo | Garcia-Marcos, Mikel | Garmyn, Marjan | Gartel, Andrei L. | Gatti, Evelina | Gautel, Mathias | Gawriluk, Thomas R. | Gegg, Matthew E. | Geng, Jiefei | Germain, Marc | Gestwicki, Jason E. | Gewirtz, David A. | Ghavami, Saeid | Ghosh, Pradipta | Giammarioli, Anna M. | Giatromanolaki, Alexandra N. | Gibson, Spencer B. | Gilkerson, Robert W. | Ginger, Michael L. | Ginsberg, Henry N. | Golab, Jakub | Goligorsky, Michael S. | Golstein, Pierre | Gomez-Manzano, Candelaria | Goncu, Ebru | Gongora, Céline | Gonzalez, Claudio D. | Gonzalez, Ramon | González-Estévez, Cristina | González-Polo, Rosa Ana | Gonzalez-Rey, Elena | Gorbunov, Nikolai V. | Gorski, Sharon | Goruppi, Sandro | Gottlieb, Roberta A. | Gozuacik, Devrim | Granato, Giovanna Elvira | Grant, Gary D. | Green, Kim N. | Gregorc, Ales | Gros, Frédéric | Grose, Charles | Grunt, Thomas W. | Gual, Philippe | Guan, Jun-Lin | Guan, Kun-Liang | Guichard, Sylvie M. | Gukovskaya, Anna S. | Gukovsky, Ilya | Gunst, Jan | Gustafsson, Åsa B. | Halayko, Andrew J. | Hale, Amber N. | Halonen, Sandra K. | Hamasaki, Maho | Han, Feng | Han, Ting | Hancock, Michael K. | Hansen, Malene | Harada, Hisashi | Harada, Masaru | Hardt, Stefan E. | Harper, J. Wade | Harris, Adrian L. | Harris, James | Harris, Steven D. | Hashimoto, Makoto | Haspel, Jeffrey A. | Hayashi, Shin-ichiro | Hazelhurst, Lori A. | He, Congcong | He, You-Wen | Hébert, Marie-Josée | Heidenreich, Kim A. | Helfrich, Miep H. | Helgason, Gudmundur V. | Henske, Elizabeth P. | Herman, Brian | Herman, Paul K. | Hetz, Claudio | Hilfiker, Sabine | Hill, Joseph A. | Hocking, Lynne J. | Hofman, Paul | Hofmann, Thomas G. | Höhfeld, Jörg | Holyoake, Tessa L. | Hong, Ming-Huang | Hood, David A. | Hotamisligil, Gökhan S. | Houwerzijl, Ewout J. | Høyer-Hansen, Maria | Hu, Bingren | Hu, Chien-an A. | Hu, Hong-Ming | Hua, Ya | Huang, Canhua | Huang, Ju | Huang, Shengbing | Huang, Wei-Pang | Huber, Tobias B. | Huh, Won-Ki | Hung, Tai-Ho | Hupp, Ted R. | Hur, Gang Min | Hurley, James B. | Hussain, Sabah N.A. | Hussey, Patrick J. | Hwang, Jung Jin | Hwang, Seungmin | Ichihara, Atsuhiro | Ilkhanizadeh, Shirin | Inoki, Ken | Into, Takeshi | Iovane, Valentina | Iovanna, Juan L. | Ip, Nancy Y. | Isaka, Yoshitaka | Ishida, Hiroyuki | Isidoro, Ciro | Isobe, Ken-ichi | Iwasaki, Akiko | Izquierdo, Marta | Izumi, Yotaro | Jaakkola, Panu M. | Jäättelä, Marja | Jackson, George R. | Jackson, William T. | Janji, Bassam | Jendrach, Marina | Jeon, Ju-Hong | Jeung, Eui-Bae | Jiang, Hong | Jiang, Hongchi | Jiang, Jean X. | Jiang, Ming | Jiang, Qing | Jiang, Xuejun | Jiang, Xuejun | Jiménez, Alberto | Jin, Meiyan | Jin, Shengkan V. | Joe, Cheol O. | Johansen, Terje | Johnson, Daniel E. | Johnson, Gail V.W. | Jones, Nicola L. | Joseph, Bertrand | Joseph, Suresh K. | Joubert, Annie M. | Juhász, Gábor | Juillerat-Jeanneret, Lucienne | Jung, Chang Hwa | Jung, Yong-Keun | Kaarniranta, Kai | Kaasik, Allen | Kabuta, Tomohiro | Kadowaki, Motoni | Kågedal, Katarina | Kamada, Yoshiaki | Kaminskyy, Vitaliy O. | Kampinga, Harm H. | Kanamori, Hiromitsu | Kang, Chanhee | Kang, Khong Bee | Kang, Kwang Il | Kang, Rui | Kang, Yoon-A | Kanki, Tomotake | Kanneganti, Thirumala-Devi | Kanno, Haruo | Kanthasamy, Anumantha G. | Kanthasamy, Arthi | Karantza, Vassiliki | Kaushal, Gur P. | Kaushik, Susmita | Kawazoe, Yoshinori | Ke, Po-Yuan | Kehrl, John H. | Kelekar, Ameeta | Kerkhoff, Claus | Kessel, David H. | Khalil, Hany | Kiel, Jan A.K.W. | Kiger, Amy A. | Kihara, Akio | Kim, Deok Ryong | Kim, Do-Hyung | Kim, Dong-Hou | Kim, Eun-Kyoung | Kim, Hyung-Ryong | Kim, Jae-Sung | Kim, Jeong Hun | Kim, Jin Cheon | Kim, John K. | Kim, Peter K. | Kim, Seong Who | Kim, Yong-Sun | Kim, Yonghyun | Kimchi, Adi | Kimmelman, Alec C. | King, Jason S. | Kinsella, Timothy J. | Kirkin, Vladimir | Kirshenbaum, Lorrie A. | Kitamoto, Katsuhiko | Kitazato, Kaio | Klein, Ludger | Klimecki, Walter T. | Klucken, Jochen | Knecht, Erwin | Ko, Ben C.B. | Koch, Jan C. | Koga, Hiroshi | Koh, Jae-Young | Koh, Young Ho | Koike, Masato | Komatsu, Masaaki | Kominami, Eiki | Kong, Hee Jeong | Kong, Wei-Jia | Korolchuk, Viktor I. | Kotake, Yaichiro | Koukourakis, Michael I. | Flores, Juan B. 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Angus | Meijer, Alfred J. | Meisler, Miriam H. | Meléndez, Alicia | Melia, Thomas J. | Melino, Gerry | Mena, Maria A. | Menendez, Javier A. | Menna-Barreto, Rubem F. S. | Menon, Manoj B. | Menzies, Fiona M. | Mercer, Carol A. | Merighi, Adalberto | Merry, Diane E. | Meschini, Stefania | Meyer, Christian G. | Meyer, Thomas F. | Miao, Chao-Yu | Miao, Jun-Ying | Michels, Paul A.M. | Michiels, Carine | Mijaljica, Dalibor | Milojkovic, Ana | Minucci, Saverio | Miracco, Clelia | Miranti, Cindy K. | Mitroulis, Ioannis | Miyazawa, Keisuke | Mizushima, Noboru | Mograbi, Baharia | Mohseni, Simin | Molero, Xavier | Mollereau, Bertrand | Mollinedo, Faustino | Momoi, Takashi | Monastyrska, Iryna | Monick, Martha M. | Monteiro, Mervyn J. | Moore, Michael N. | Mora, Rodrigo | Moreau, Kevin | Moreira, Paula I. | Moriyasu, Yuji | Moscat, Jorge | Mostowy, Serge | Mottram, Jeremy C. | Motyl, Tomasz | Moussa, Charbel E.-H. | Müller, Sylke | Muller, Sylviane | Münger, Karl | Münz, Christian | Murphy, Leon O. | Murphy, Maureen E. | Musarò, Antonio | Mysorekar, Indira | Nagata, Eiichiro | Nagata, Kazuhiro | Nahimana, Aimable | Nair, Usha | Nakagawa, Toshiyuki | Nakahira, Kiichi | Nakano, Hiroyasu | Nakatogawa, Hitoshi | Nanjundan, Meera | Naqvi, Naweed I. | Narendra, Derek P. | Narita, Masashi | Navarro, Miguel | Nawrocki, Steffan T. | Nazarko, Taras Y. | Nemchenko, Andriy | Netea, Mihai G. | Neufeld, Thomas P. | Ney, Paul A. | Nezis, Ioannis P. | Nguyen, Huu Phuc | Nie, Daotai | Nishino, Ichizo | Nislow, Corey | Nixon, Ralph A. | Noda, Takeshi | Noegel, Angelika A. | Nogalska, Anna | Noguchi, Satoru | Notterpek, Lucia | Novak, Ivana | Nozaki, Tomoyoshi | Nukina, Nobuyuki | Nürnberger, Thorsten | Nyfeler, Beat | Obara, Keisuke | Oberley, Terry D. | Oddo, Salvatore | Ogawa, Michinaga | Ohashi, Toya | Okamoto, Koji | Oleinick, Nancy L. | Oliver, F. Javier | Olsen, Laura J. | Olsson, Stefan | Opota, Onya | Osborne, Timothy F. | Ostrander, Gary K. | Otsu, Kinya | Ou, Jing-hsiung James | Ouimet, Mireille | Overholtzer, Michael | Ozpolat, Bulent | Paganetti, Paolo | Pagnini, Ugo | Pallet, Nicolas | Palmer, Glen E. | Palumbo, Camilla | Pan, Tianhong | Panaretakis, Theocharis | Pandey, Udai Bhan | Papackova, Zuzana | Papassideri, Issidora | Paris, Irmgard | Park, Junsoo | Park, Ohkmae K. | Parys, Jan B. | Parzych, Katherine R. | Patschan, Susann | Patterson, Cam | Pattingre, Sophie | Pawelek, John M. | Peng, Jianxin | Perlmutter, David H. | Perrotta, Ida | Perry, George | Pervaiz, Shazib | Peter, Matthias | Peters, Godefridus J. | Petersen, Morten | Petrovski, Goran | Phang, James M. | Piacentini, Mauro | Pierre, Philippe | Pierrefite-Carle, Valérie | Pierron, Gérard | Pinkas-Kramarski, Ronit | Piras, Antonio | Piri, Natik | Platanias, Leonidas C. | Pöggeler, Stefanie | Poirot, Marc | Poletti, Angelo | Poüs, Christian | Pozuelo-Rubio, Mercedes | Prætorius-Ibba, Mette | Prasad, Anil | Prescott, Mark | Priault, Muriel | Produit-Zengaffinen, Nathalie | Progulske-Fox, Ann | Proikas-Cezanne, Tassula | Przedborski, Serge | Przyklenk, Karin | Puertollano, Rosa | Puyal, Julien | Qian, Shu-Bing | Qin, Liang | Qin, Zheng-Hong | Quaggin, Susan E. | Raben, Nina | Rabinowich, Hannah | Rabkin, Simon W. | Rahman, Irfan | Rami, Abdelhaq | Ramm, Georg | Randall, Glenn | Randow, Felix | Rao, V. Ashutosh | Rathmell, Jeffrey C. | Ravikumar, Brinda | Ray, Swapan K. | Reed, Bruce H. | Reed, John C. | Reggiori, Fulvio | Régnier-Vigouroux, Anne | Reichert, Andreas S. | Reiners, John J. | Reiter, Russel J. | Ren, Jun | Revuelta, José L. | Rhodes, Christopher J. | Ritis, Konstantinos | Rizzo, Elizete | Robbins, Jeffrey | Roberge, Michel | Roca, Hernan | Roccheri, Maria C. | Rocchi, Stephane | Rodemann, H. Peter | Rodríguez de Córdoba, Santiago | Rohrer, Bärbel | Roninson, Igor B. | Rosen, Kirill | Rost-Roszkowska, Magdalena M. | Rouis, Mustapha | Rouschop, Kasper M.A. | Rovetta, Francesca | Rubin, Brian P. | Rubinsztein, David C. | Ruckdeschel, Klaus | Rucker, Edmund B. | Rudich, Assaf | Rudolf, Emil | Ruiz-Opazo, Nelson | Russo, Rossella | Rusten, Tor Erik | Ryan, Kevin M. | Ryter, Stefan W. | Sabatini, David M. | Sadoshima, Junichi | Saha, Tapas | Saitoh, Tatsuya | Sakagami, Hiroshi | Sakai, Yasuyoshi | Salekdeh, Ghasem Hoseini | Salomoni, Paolo | Salvaterra, Paul M. | Salvesen, Guy | Salvioli, Rosa | Sanchez, Anthony M.J. | Sánchez-Alcázar, José A. | Sánchez-Prieto, Ricardo | Sandri, Marco | Sankar, Uma | Sansanwal, Poonam | Santambrogio, Laura | Saran, Shweta | Sarkar, Sovan | Sarwal, Minnie | Sasakawa, Chihiro | Sasnauskiene, Ausra | Sass, Miklós | Sato, Ken | Sato, Miyuki | Schapira, Anthony H.V. | Scharl, Michael | Schätzl, Hermann M. | Scheper, Wiep | Schiaffino, Stefano | Schneider, Claudio | Schneider, Marion E. | Schneider-Stock, Regine | Schoenlein, Patricia V. | Schorderet, Daniel F. | Schüller, Christoph | Schwartz, Gary K. | Scorrano, Luca | Sealy, Linda | Seglen, Per O. | Segura-Aguilar, Juan | Seiliez, Iban | Seleverstov, Oleksandr | Sell, Christian | Seo, Jong Bok | Separovic, Duska | Setaluri, Vijayasaradhi | Setoguchi, Takao | Settembre, Carmine | Shacka, John J. | Shanmugam, Mala | Shapiro, Irving M. | Shaulian, Eitan | Shaw, Reuben J. | Shelhamer, James H. | Shen, Han-Ming | Shen, Wei-Chiang
Autophagy  2012;8(4):445-544.
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
doi:10.4161/auto.19496
PMCID: PMC3404883  PMID: 22966490
LC3; autolysosome; autophagosome; flux; lysosome; phagophore; stress; vacuole
22.  Common Severe Infections in Chronic Granulomatous Disease 
Chronic granulomatous disease is a genetic immunodeficiency characterized by a limited spectrum of recurrent bacterial and fungal infections. Genetically determined superoxide production is linked to overall survival as well as severity of infections.
Background. Chronic granulomatous disease (CGD) is due to defective nicotinamide adenine dinucleotide phosphate oxidase activity and characterized by recurrent infections with a limited spectrum of bacteria and fungi as well as inflammatory complications. To understand the impact of common severe infections in CGD, we examined the records of 268 patients followed at a single center over 4 decades.
Methods. All patients had confirmed diagnoses of CGD, and genotype was determined where possible. Medical records were excerpted into a standard format. Microbiologic analyses were restricted to Staphylococcus, Burkholderia, Serratia, Nocardia, and Aspergillus.
Results. Aspergillus incidence was estimated at 2.6 cases per 100 patient-years; Burkholderia, 1.06 per 100 patient-years; Nocardia, 0.81 per 100 patient-years; Serratia, 0.98 per 100 patient-years, and severe Staphylococcus infection, 1.44 per 100 patient-years. Lung infection occurred in 87% of patients, whereas liver abscess occurred in 32%. Aspergillus incidence was 55% in the lower superoxide-producing quartiles (quartiles 1 and 2) but only 41% in the higher quartiles (rate ratio, <0.0001). Aspergillus and Serratia were somewhat more common in lower superoxide producing gp91phox deficiency. The median age at death has increased from 15.53 years before 1990 to 28.12 years in the last decade. Fungal infection carried a higher risk of mortality than bacterial infection and was the most common cause of death (55%).Gastrointestinal complications were not associated with either infection or mortality.
Conclusions. Fungal infections remain a major determinant of survival in CGD. X-linked patients generally had more severe disease, and this was generally in those with lower residual superoxide production. Survival in CGD has increased over the years, but infections are still major causes of morbidity and mortality.
doi:10.1093/cid/ciu1154
PMCID: PMC4400412  PMID: 25537876
bacterial infection; fungal infection; CGD; superoxide production; survival
23.  Differential Longitudinal Decline on the Mini-Mental State Examination in Frontotemporal Lobar Degeneration and Alzheimer's Disease 
Alzheimer disease and associated disorders  2013;27(4):10.1097/WAD.0b013e31827bdc6f.
Objective
To examine how phenotype affects longitudinal decline on the Mini-Mental State Examination (MMSE) in patients with frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD)
Background
The MMSE is the most commonly administered assessment for dementia severity; however, the effects of phenotype on longitudinal MMSE performance in FTLD and AD have not been extensively studied.
Methods
Data from 185 patients diagnosed with AD (n=106) and three FTLD (n=79) phenotypes (behavioral variant frontotemporal dementia [bvFTD], nonfluent agrammatic variant of primary progressive aphasia [nfaPPA], and semantic variant PPA [svPPA]) were collected for up to 52 months since initial evaluation.
Results
Differential rates of decline were noted in that MMSE scores declined more precipitously for AD and svPPA compared to bvFTD and nfaPPA patients (p=0.001). The absolute 4-year MMSE decline given median baseline MMSE for bvFTD (14.67, 95% confidence interval [CI]: 14.63-14.71) and nfaPPA (11.02, 95% CI: 10.98-11.06) were lower than svPPA (22.32, 95% CI: 22.29-22.34) or AD (22.24, 95% CI: 22.22-22.26).
Conclusions
These data suggest that within-group AD and FTLD phenotypes present distinct patterns of longitudinal decline on the MMSE. MMSE may not be adequately sensitive to track disease progression in some phenotypes of FTLD.
doi:10.1097/WAD.0b013e31827bdc6f
PMCID: PMC3648632  PMID: 23314064
MMSE; Alzheimer's disease; frontotemporal lobe dementia; longitudinal assessment
24.  Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac–derived macrophages 
The Journal of Experimental Medicine  2012;209(6):1167-1181.
Langerhans cell precursors initially arise from yolk sac progenitors, but are later superseded by fetal liver monocytes.
Langerhans cells (LCs) are the dendritic cells (DCs) of the epidermis, forming one of the first hematopoietic lines of defense against skin pathogens. In contrast to other DCs, LCs arise from hematopoietic precursors that seed the skin before birth. However, the origin of these embryonic precursors remains unclear. Using in vivo lineage tracing, we identify a first wave of yolk sac (YS)–derived primitive myeloid progenitors that seed the skin before the onset of fetal liver hematopoiesis. YS progenitors migrate to the embryo proper, including the prospective skin, where they give rise to LC precursors, and the brain rudiment, where they give rise to microglial cells. However, in contrast to microglia, which remain of YS origin throughout life, YS-derived LC precursors are largely replaced by fetal liver monocytes during late embryogenesis. Consequently, adult LCs derive predominantly from fetal liver monocyte-derived cells with a minor contribution of YS-derived cells. Altogether, we establish that adult LCs have a dual origin, bridging early embryonic and late fetal myeloid development.
doi:10.1084/jem.20120340
PMCID: PMC3371735  PMID: 22565823
25.  Human Tissues Contain CD141hi Cross-Presenting Dendritic Cells with Functional Homology to Mouse CD103+ Nonlymphoid Dendritic Cells 
Immunity  2012;37(1):60-73.
Summary
Dendritic cell (DC)-mediated cross-presentation of exogenous antigens acquired in the periphery is critical for the initiation of CD8+ T cell responses. Several DC subsets are described in human tissues but migratory cross-presenting DCs have not been isolated, despite their potential importance in immunity to pathogens, vaccines, and tumors and tolerance to self. Here, we identified a CD141hi DC present in human interstitial dermis, liver, and lung that was distinct from the majority of CD1c+ and CD14+ tissue DCs and superior at cross-presenting soluble antigens. Cutaneous CD141hi DCs were closely related to blood CD141+ DCs, and migratory counterparts were found among skin-draining lymph node DCs. Comparative transcriptomic analysis with mouse showed tissue DC subsets to be conserved between species and permitted close alignment of human and mouse DC subsets. These studies inform the rational design of targeted immunotherapies and facilitate translation of mouse functional DC biology to the human setting.
Graphical Abstract
Highlights
► Human tissues contain CD1c+ DCs, CD14+ DCs, and a CD141hi cross-presenting DC subset ► CD141hi DCs migrate to draining lymph nodes and probably arise from blood CD141+ DCs ► Human tissue CD141hi DCs are homologous to mouse CD103+ or CD8+ DCs ► Human tissue CD1c+ DCs are homologous to mouse CD4+ DCs
doi:10.1016/j.immuni.2012.04.012
PMCID: PMC3476529  PMID: 22795876

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